Nitric Oxide Synthase-Independent Generation of Nitric Oxide in Muscle Ischemia–Reperfusion Injury

Nitric Oxide ◽  
2000 ◽  
Vol 4 (6) ◽  
pp. 541-545 ◽  
Author(s):  
D.A. Lepore
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Muscle Ischemia ◽  
Oxide Synthase

Nitric Oxide Synthase-Independent Generation of Nitric Oxide in Rat Skeletal Muscle Ischemia-Reperfusion Injury

Nitric Oxide ◽  
1999 ◽  
Vol 3 (1) ◽  
pp. 75-84 ◽  
Author(s):  
D.A. Lepore ◽  
A.V. Kozlov ◽  
A.G. Stewart ◽  
J.V. Hurley ◽  
W.A. Morrison ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Nitric Oxide Synthase ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rat Skeletal Muscle ◽  
Muscle Ischemia ◽  
Oxide Synthase

scholarly journals Inhibition of inducible nitric oxide synthase reduces renal ischemia/reperfusion injury

2002 ◽  
Vol 61 (3) ◽  
pp. 862-871 ◽  
Author(s):  
Prabal K. Chatterjee ◽  
Nimesh S.A. Patel ◽  
Espen O. Kvale ◽  
Salvatore Cuzzocrea ◽  
Paul A.J. Brown ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Reperfusion Injury ◽  
Inducible Nitric Oxide Synthase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Renal Ischemia Reperfusion Injury ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals ERK phosphorylation mediates sildenafil-induced myocardial protection against ischemia-reperfusion injury in mice

2009 ◽  
Vol 296 (5) ◽  
pp. H1236-H1243 ◽  
Author(s):  
Anindita Das ◽  
Fadi N. Salloum ◽  
Lei Xi ◽  
Yuan J. Rao ◽  
Rakesh C. Kukreja
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Infarct Size ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Global Ischemia ◽  
Erk Phosphorylation ◽  
Gsk 3Β ◽  
Oxide Synthase

Sildenafil, a selective inhibitor of phosphodiesterase type 5, induces powerful protection against myocardial ischemia-reperfusion injury through activation of cGMP-dependent protein kinase (PKG). We further hypothesized that PKG-dependent activation of survival kinase ERK may play a causative role in sildenafil-induced cardioprotection via induction of endothelial nitric oxide synthase (eNOS)/inducible nitric oxide synthase (iNOS) and Bcl-2. Our results show that acute intracoronary infusion of sildenafil in Langendorff isolated mouse hearts before global ischemia-reperfusion significantly reduced myocardial infarct size (from 29.4 ± 2.4% to 15.9 ± 3.0%; P < 0.05). Cotreatment with ERK inhibitor PD98059 abrogated sildenafil-induced protection (31.8 ± 4.4%). To further evaluate the role of ERK in delayed cardioprotection, mice were treated with sildenafil (ip) 24 h before global ischemia-reperfusion. PD98059 was administered (ip) 30 min before sildenafil treatment. Infarct size was reduced from 27.6 ± 3.3% in controls to 7.1 ± 1.5% in sildenafil-treated mice ( P < 0.05). The delayed protective effect of sildenafil was also abolished by PD98059 (22.5 ± 2.3%). Western blots revealed that sildenafil significantly increased phosphorylation of ERK1/2 and GSK-3β and induced iNOS, eNOS, Bcl-2, and PKG activity in the heart 24 h after treatment. PD98059 inhibited the enhanced expression of iNOS, eNOS, and Bcl-2 and the phosphorylation of GSK-3β. PD98059 had no effect on the sildenafil-induced activation of PKG. We conclude that these studies provide first direct evidence that PKG-dependent ERK phosphorylation is indispensable for the induction of eNOS/iNOS and Bcl-2 and the resulting cardioprotection by sildenafil.

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